A Review of the Treatment Options in Recurrent Glioblastoma: Focus on Bevacizumab

2011 ◽  
Vol 3 ◽  
pp. 79-92
Author(s):  
Raymund L. Yong and John K. Park
Keyword(s):  
Treatment Options ◽  
Recurrent Glioblastoma

scholarly journals RADT-23. IMPACT OF REIRRADIATION UTILIZING STEREOTACTIC RADIOSURGERY ON RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
High Performance ◽  
Performance Status ◽  
Treatment Options ◽  
Methylation Status ◽  
Initial Therapy ◽  
Recurrent Glioblastoma ◽  
Control Group ◽  
The Impact

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P < 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P< 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.

scholarly journals Multiomics profiling of paired primary and recurrent glioblastoma patient tissues

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Lennard J M Dekker ◽  
Nynke M Kannegieter ◽  
Femke Haerkens ◽  
Emma Toth ◽  
Johan M Kros ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Snare Complex ◽  
Tumor Type ◽  
Tissue Samples ◽  
Individual Patient Level ◽  
Individual Level ◽  
The Individual ◽  
Recurrent Gbm

Abstract Background Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relates to the failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multiomics approach using transcriptomics, proteomics, and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxinA (synaptogenesis) and afatinib (ERBB4 signaling). Afatinib is currently in clinical trials for GBM. Conclusions A large variation on all omics levels exists between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multiomics approach offers the potential to identify affected pathways on the individual patient level and select treatment options.

scholarly journals Treatment options for recurrent glioblastoma: a network meta-analysis

2020 ◽  
Author(s):  
Theresa A Lawrie ◽  
Catherine McBain ◽  
Ewelina Rogozińska ◽  
Ashleigh Kernohan ◽  
Tomos Robinson ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Treatment Options ◽  
Recurrent Glioblastoma

Phase I study of PD-L1 inhibition with avelumab and laser interstitial thermal therapy in patients with recurrent glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2074-TPS2074 ◽  
Author(s):  
Adilia Hormigo ◽  
John Mandeli ◽  
Constantinos Hadjipanayis ◽  
Sacha Gnjatic ◽  
Seunghee Kim-Schulze ◽  
...  
Keyword(s):  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Thermal Therapy ◽  
Successful Implementation ◽  
Open Label ◽  
Stage Design ◽  
Laser Interstitial Thermal Therapy ◽  
Dismal Prognosis ◽  
Mri Guided ◽  
Clinical Trial Information

TPS2074 Background: Glioblastoma (GBM) the most frequent malignant brain tumor in the adult has a dismal prognosis and limited treatment options. Current advances have highlighted how tumors and specifically GBM evade the immune system by exploiting the mechanisms of tolerance and inducing local and systemic immunosuppression. Another hurdle in the treatment of GBM is the blood-brain barrier (BBB). Recent work suggests that MRI-guided laser interstitial thermal therapy (LITT) can increase the permeability of the BBB and may have an abscopal effect. Therefore, utilizing MRI-guided LITT, a potential immunogenic cell death-inducing procedure that disrupts the BBB and makes Avelumab a PD-L1 monoclonal antibody being more accessible to GBM tumors, seem a valid approach for immunomodulation and successful implementation of a combined regimen to treat brain cancer. Methods: This is a prospective non-randomized open label to characterize the tolerability and safety profile of Avelumab in combination with LITT in patients with recurrent glioblastoma who were treated with radiation therapy with concurrent Temozolomide chemotherapy at diagnosis, and whose tumor at recurrence measures less then 3 cm3. Avelumab is administered within a week after real-time MRI-guided LITT therapy and every 2 weeks thereafter. On part A patients are treated with intravenous Avelumab alone and on part B patients receive Avelumab in combination with MRI-guided LITT. Part A completed enrollment without DLT. Enrollment on part B began in October 2018. A Simon minimax two-stage design is being used for efficacy. Toxicity will be scored using the NCI-CTCAE 4.03 criteria. Blood samples and tumor tissue will be collected for correlative studies. Quantification of the changes in inflammatory and immunosuppressive profiles across time points for patients receiving treatment with Avelumab will be obtained. This information will instruct future immunotherapy approaches to treat GBM and the rational for those combinations. Clinical trial information: NCT03341806.

scholarly journals TMIC-41. PROSTATE SPECIFIC MEMBRANE ANTIGEN EXPRESSION IN PRIMARY AND RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi256-vi256
Author(s):  
Mathew Lozinski ◽  
Michael Fay ◽  
Nikola Bowden ◽  
Moira Graves ◽  
Paul Tooney
Keyword(s):  
Blood Vessels ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
High Expression ◽  
Prostate Specific Membrane Antigen ◽  
Primary Glioblastoma ◽  
Microvascular Proliferation ◽  
Significant Difference ◽  
Specific Membrane ◽  
Psma Expression

Abstract Patients with glioblastoma almost always suffer a recurrence of an aggressive treatment resistant tumour and succumb within months highlighting the need to develop treatment options for recurrent glioblastoma. One potential target is prostate specific membrane antigen (PSMA) expressed on the new vessels in primary glioblastoma tumours. This study compared the expression of PSMA in primary and recurrent glioblastoma tumours. Formalin-fixed paraffin-embedded sections of primary and matched recurrent tumours from 13 patients with glioblastoma were processed for PSMA immunohistochemical labelling. PSMA expression was scored from digitally scanned sections using a categorical system (Total PSMA expression = PSMA label intensity (0–3) x percent PSMA-positive blood vessels). Little PSMA labelling was observed in any adjacent ‘unaffected’ brain tissue. PSMA was localised to blood vessels including those displaying microvascular proliferation in 12/13 primary and 9/13 recurrent glioblastoma tumours. Total PSMA expression scores ranged from 0 – 230 (maximum score = 300) and was divided into low and high expression based on a median split (median = 57) of PSMA expression across all tumours. Regression analysis showed a significant difference in PSMA expression between primary and recurrent glioblastoma (p = 0.04) with PSMA being highly expressed in ~70% of primary and only 31% of recurrent glioblastoma. Three cases displayed high expression in both primary and recurrent glioblastoma and one case had no PSMA expression at all. In conclusion, whilst higher expression of PSMA was detected in more primary tumours, 70%+ of all primary and recurrent tumours expressed PSMA to some extent adding evidence that this may be a useful target for treatment of glioblastoma. Larger cohorts and other techniques for detecting PSMA are needed to provide further evidence for PSMA’s utility as a target and to further define which glioblastoma patients are most likely to benefit from this approach.

Recurrent glioblastoma multiforme: a review of natural history and management options

2006 ◽  
Vol 20 (4) ◽  
pp. E3 ◽  
Author(s):  
Lewis C. Hou ◽  
Anand Veeravagu ◽  
Andrew R. Hsu ◽  
Victor C. K. Tse
Keyword(s):  
Glioblastoma Multiforme ◽  
Natural History ◽  
Research Effort ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Management Options ◽  
Fatal Disease ◽  
The Past ◽  
Recurrent Gbm

✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.

scholarly journals Nonsurgical treatment of recurrent glioblastoma

2015 ◽  
Vol 22 (4) ◽  
pp. 273 ◽  
Author(s):  
O. Gallego
Keyword(s):  
Standard Treatment ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Response Assessment ◽  
Recurrent Glioblastoma ◽  
Second Line ◽  
Glioblastoma Recurrence ◽  
Epidermal Growth ◽  
Almost All ◽  
New Surgery

Standard treatment for glioblastoma multiforme is surgery followed by radiotherapy and chemotherapy, generally with temozolomide. However, disease recurs in almost all patients. Diagnosis of progression is complex given the possibility of pseudoprogression.The Response Assessment in Neuro-Oncology criteria increase the sensitivity for detecting progression. Most patients will not be candidates for new surgery or re-irradiation, and anticancer drugs are the most common approach for second-line treatment, if the patient’s condition allows. Antiangiogenics, inhibitors of the epidermal growth factor receptor, nitrosoureas, and re-treatment with temozolomide have been studied in the second line, but a standard therapy has not yet been established. This review considers currently available medical treatment options for patients with glioblastoma recurrence.

scholarly journals Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma – safety and efficacy

2021 ◽  
Author(s):  
Leszek Królicki ◽  
Frank Bruchertseifer ◽  
Jolanta Kunikowska ◽  
Henryk Koziara ◽  
Dariusz Pawlak ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Dose Escalation ◽  
Liver Toxicity ◽  
Performance Status ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Mri Imaging ◽  
Dose Escalation Study ◽  
Good Tolerability ◽  
Grade 3

Abstract Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [225Ac]Ac-DOTA-SP therapy. Material and methods A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1–6 doses of [225Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging. Results Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [225Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [225Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [225Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups. Conclusions Treatment of recurrent glioblastoma with [225Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.

scholarly journals Recurrent Glioblastoma: From Molecular Landscape to New Treatment Perspectives

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 47
Author(s):  
Cristina Birzu ◽  
Pim French ◽  
Mario Caccese ◽  
Giulia Cerretti ◽  
Ahmed Idbaih ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Recurrent Glioblastoma ◽  
Molecular Characteristics ◽  
Specific Gene ◽  
Primary Tumors ◽  
First Line Therapy

Glioblastoma is the most frequent and aggressive form among malignant central nervous system primary tumors in adults. Standard treatment for newly diagnosed glioblastoma consists in maximal safe resection, if feasible, followed by radiochemotherapy and adjuvant chemotherapy with temozolomide; despite this multimodal treatment, virtually all glioblastomas relapse. Once tumors progress after first-line therapy, treatment options are limited and management of recurrent glioblastoma remains challenging. Loco-regional therapy with re-surgery or re-irradiation may be evaluated in selected cases, while traditional systemic therapy with nitrosoureas and temozolomide rechallenge showed limited efficacy. In recent years, new clinical trials using, for example, regorafenib or a combination of tyrosine kinase inhibitors and immunotherapy were performed with promising results. In particular, molecular targeted therapy could show efficacy in selected patients with specific gene mutations. Nonetheless, some molecular characteristics and genetic alterations could change during tumor progression, thus affecting the efficacy of precision medicine. We therefore reviewed the molecular and genomic landscape of recurrent glioblastoma, the strategy for clinical management and the major phase I-III clinical trials analyzing recent drugs and combination regimens in these patients.

scholarly journals First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingtang Lin ◽  
Teer Ba ◽  
Jinyuan Ho ◽  
Dandan Chen ◽  
Ye Cheng ◽  
...  
Keyword(s):  
T Cells ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Human Trial ◽  
Car T Cells ◽  
Tumor Associated Antigen ◽  
Patient Reported ◽  
Car T ◽  
Starting Dose ◽  
Positive Recurrent

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 03423992

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